Massey T E, Walker R M, McElligott T F, Racz W J
Toxicology. 1987 Feb;43(2):149-60. doi: 10.1016/0300-483x(87)90005-9.
Incubation of freshly isolated mouse hepatocytes with 0.5 or 1.0 mM furosemide caused a depletion of cellular acid soluble sulfhydryls to approximately 20-30% of control over the course of 4.5 h. The depletion was accompanied by a reduction in cell viability (indicated by the lactate dehydrogenase latency test) which was significant (P less than 0.05) for 0.5 mM but not for 1.0 mM furosemide at 4.5 h. Ultrastructurally, 0.5 or 1.0 mM furosemide caused cytoplasmic changes including loss of glycogen, disaggregation of polyribosomes, vesiculation of endoplasmic reticulum, and occasional appearance of lamellar bodies consisting of concentric arrays of paired smooth membranes. These concentrations of furosemide also caused cell surface changes, including loss of microvilli, development of an irregular shape compared to the spherical appearance of untreated hepatocytes, and the development of occasional blebs. The appearance of pale staining hydropic cells was indicative of the final stages of cell death. N-Acetylcysteine (6.0 mM) was effective at preventing the depletion of soluble sulfhydryls, the loss of viability, and the ultrastructural effects of 0.5 or 1.0 mM furosemide, suggesting a role for soluble sulfhydryls in the pathogenesis of furosemide hepatotoxicity.
将新鲜分离的小鼠肝细胞与0.5或1.0 mM速尿一起孵育4.5小时后，细胞内酸溶性巯基耗竭至对照水平的约20 - 30%。这种耗竭伴随着细胞活力的降低（通过乳酸脱氢酶潜伏试验表明），在4.5小时时，0.5 mM速尿导致的细胞活力降低具有统计学意义（P小于0.05），而1.0 mM速尿则未导致显著降低。在超微结构上，0.5或1.0 mM速尿引起细胞质变化，包括糖原丢失、多核糖体解聚、内质网形成小泡，以及偶尔出现由成对光滑膜同心排列组成的板层小体。这些浓度的速尿还引起细胞表面变化，包括微绒毛丧失、与未处理肝细胞的球形外观相比形状不规则，以及偶尔出现泡状突起。淡染的水肿细胞的出现表明细胞死亡的最后阶段。N - 乙酰半胱氨酸（6.0 mM）可有效防止0.5或1.0 mM速尿引起的可溶性巯基耗竭、活力丧失及超微结构变化，提示可溶性巯基在速尿肝毒性发病机制中起作用。
